2012, Number 3
<< Back Next >>
Ann Hepatol 2012; 11 (3)
Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of esophageal variceal bleeding
Funakoshi N, Duny Y, Jean-Christophe V, Ségalas-Largey F, Flori N, Bismuth M, Jean-Pierre D, Blanc P
Language: English
References: 50
Page: 369-383
PDF size: 253.91 Kb.
ABSTRACT
Aim. To perform an updated meta-analysis comparing β-blockers (BB) with endoscopic variceal banding
ligation (EVBL) in the primary prophylaxis of esophageal variceal bleeding.
Material and methods. Randomized
controlled trials were identified through electronic databases, article reference lists and conference
proceedings. Analysis was performed using both fixed-effect and random-effect models. Heterogeneity and
publication bias were systematically taken into account. Main outcomes were variceal bleeding rates and
all-cause mortality, calculated overall and at 6, 12, 18 and 24 months.
Results. 19 randomized controlled
trials were analyzed including a total of 1,483 patients. Overall bleeding rates were significantly lower for
the EVBL group: odds ratio (OR) 2.06, 95% confidence interval (CI) [1.55-2.73],
p‹ 0.0001, without evidence
of publication bias. Bleeding rates were also significantly lower at 18 months (OR 2.20, 95% CI [1.04-4.60],
p = 0.04), but publication bias was detected. When only high quality trials were taken into account, results
for bleeding rates were no longer significant. No significant difference was found for either bleedingrelated
mortality or for all-cause mortality overall or at 6, 12, 18 or 24 months. BB were associated with
more frequent severe adverse events (OR 2.61, 95% CI 1.60-4.40,
P ‹ 0.0001) whereas fatal adverse events
were more frequent with EVBL (OR 0.14, 95% CI 0.02-0.99,
p = 0.05).
Conclusion. EVBL appears to be superior
to BB in preventing the first variceal bleed, although this finding may be biased as it was not confirmed
by high quality trials. No difference was found for mortality. Current evidence is insufficient to recommend
EVBL over BB as first-line therapy.
REFERENCES
D’Amico G, Luca A. Natural history. Clinical-haemodynamic correlations. Prediction of the risk of bleeding. Baillieres Clin Gastroenterol 1997; 11: 243-56.
Gunnarsdottir SA, Olsson R, Bjornsson ES. Characteristics, prognosis and outcome of patients with oesophageal varices in a university hospital in Sweden 1994-1999. Scand J Gastroenterol 2005; 40: 1462-8.
De Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53: 762-8.
Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46: 922-38.
Garcia-Tsao G, Grace ND, Groszmann RJ, Conn HO, Bermann MM, Patrick MJ, Morse SS, et al. Short-term effects of propranolol on portal venous pressure. Hepatology 1986; 6: 101-6.
Gluud LL, Klingenberg S, Nikolova D, Gluud C. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol 2007; 102: 2842-8; Quiz 41, 49.
Tripathi D, Graham C, Hayes PC. Variceal band ligation versus beta-blockers for primary prevention of variceal bleeding: a meta-analysis. Eur J Gastroenterol Hepatol 2007; 19: 835-45.
Imperiale TF, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding. Hepatology 2001; 33: 802-7.
Khuroo MS, Khuroo NS, Farahat KL, Khuroo YS, Sofi AA, Dahab ST. Meta-analysis: endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding. Aliment Pharmacol Ther 2005; 21: 347-61.
Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley-Blackwell, 2008.
Cohen MJ, Sahar T, Benenson S, Elinav E, Brezis M, Soares- Weiser K. Antibiotic prophylaxis for spontaneous bacterial peritonitis in cirrhotic patients with ascites, without gastro- intestinal bleeding. Cochrane Database Syst Rev 2009:CD004791.
US Department of Health and Human Services: Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/ About.html 2009.
Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988; 318: 1162-73.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-88.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-58.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-34.
Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 2001; 54: 1046-55.
Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56: 455-63.
Orwin R. A fail-safe N for effect size in meta-analysis. J Educational Statistics 1983; 157-9.
Harewood GC, Baron TH, Song LM. Factors predicting success of endoscopic variceal ligation for secondary prophylaxis of esophageal variceal bleeding. J Gastroenterol Hepatol 2006; 21: 237-41.
De BK, Ghoshal UC, Das T, Santra A, Biswas PK. Endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleed: preliminary report of a randomized controlled trial. J Gastroenterol Hepatol 1999; 14: 220-4.
Sarin SK, Lamba GS, Kumar M, Misra A, Murthy NS. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med 1999; 340: 988-93.
Lui HF, Stanley AJ, Forrest EH, Jalan R, Hislop WS, Mills PR, Finlayson ND, et al. Primary prophylaxis of variceal hemorrhage: a randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate. Gastroenterology 2002; 123: 735-44.
Lo GH, Chen WC, Chen MH, Lin CP, Lo CC, Hsu PI, Cheng JS, et al. Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis. Gastrointest Endosc 2004; 59: 333-8.
Schepke M, Kleber G, Nurnberg D, Willert J, Koch L, Veltzke- Schlieker W, Hellerbrand C, et al. Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2004; 40: 65-72.
Thuluvath PJ, Maheshwari A, Jagannath S, Arepally A. A randomized controlled trial of beta-blockers versus endoscopic band ligation for primary prophylaxis: a large sample size is required to show a difference in bleeding rates. Dig Dis Sci 2005; 50: 407-10.
Jutabha R, Jensen DM, Martin P, Savides T, Han SH, Gornbein J. Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices. Gastroenterology 2005; 128: 870-81.
Psilopoulos D, Galanis P, Goulas S, Papanikolaou IS, Elefsiniotis I, Liatsos C, Sparos L, et al. Endoscopic variceal ligation vs. propranolol for prevention of first variceal bleeding: a randomized controlled trial. Eur J Gastroenterol Hepatol 2005; 17: 1111-7.
Lay CS, Tsai YT, Lee FY, Lai YL, Yu CJ, Chen CB, Peng CY. Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis. J Gastroenterol Hepatol 2006; 21: 413-9.
Norberto L, Polese L, Cillo U, Grigoletto F, Burroughs AK, Neri D, Zanus G, et al. A randomized study comparing ligation with propranolol for primary prophylaxis of variceal bleeding in candidates for liver transplantation. Liver Transpl 2007; 13: 1272-8.
Drastich P, Lata J, Petrtyl J, Bruha R, Prochazka V, Vanasek T, Zdenek P, et al. Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding. Ann Hepatol 2011; 10: 142-9.
Chen C, Sheu M, Su S. Prophylactic endoscopic variceal ligation (EVL) with multiple band ligator for esophageal varices [Abstract]. Gastroenterology 1998; 114: A1224.
Song I, Shin J, Kim I, Choi J, Lim C, Kim J, Roe I. A prospective randomized trial between the prophylactic endoscopic variceal ligation and propranolol administration for prevention of first bleeding in cirrhotic patients with high-risk esophageal varices [Abstract]. J Hepatol 2000; 32: 41.
Lopez-Acosta ME, De la Mora-Levy JG, Blancas-Valencia JM, Paz-Flores VM. Primary prophylaxis of variceal bleeding comparing propranolol versus recharging a multiple band ligator: Up to 4 years follow-up [Abstract]. Gastrointest Endosc 2002; 55: AB 195.
Gheorghe C, Gheorghe L, Vadan R, Hrehoret D, Popescu I. Prophylactic banding ligation of high risk esophageal varices in patients on the waiting list for liver transplantation: an interim report [Abstract]. J Hepatol 2002; 36: 38.
Abulfutuh A, Morsy M, Solyman A, El Hendawy S, El Desouky M, El Hadad S, Kamel M. Study of variceal band ligation, propranolol and isosorbide mononitrate in the prevention of the first variceal bleeding [Abstract]. Gastroenterology 2003;124: A780.
Abdelfattah M, Rashed M, Elfakhry A, Soliman M, Shiha G. Endoscopic variceal ligation versus pharmacologic treatment for primary prophylaxis of variceal bleeding: a randomised study [Abstract]. J Hepatol 2006; 44: S83.
Gill M, Sattar S, Khokar N. Outcomes of endoscopic variceal band ligation versus pharmacological treatment with non selective beta blocker for primary prophylaxis of variceal bleed [Abstract]. Gut 2006; 55: A308.
Perez-Ayuso RM, Valderrama S, Espinoza M, Rollan A, Sanchez R, Otarola F, Medina B, et al. Endoscopic band ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhotic patients with high risk esophageal varices. Ann Hepatol 2010; 9: 15-22.
De la Mora J, Farca-Belsaguy A, Uribe M, De Hoyos-Garza A. Ligation vs. propranolol for primary prophylaxis of variceal bleeding using a multiple band ligator and objective measurements of treatment adequacy: preliminary results [Abstract]. Gastroenterology 2000; 118: A1434-5.
Tripathi D, Ferguson JW, Kochar N, Leithead JA, Therapondos G, McAvoy NC, Stanley AJ, et al. Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology 2009; 50: 825-33.
Forrest EH, Bouchier IA, Hayes PC. Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in patients with cirrhosis. J Hepatol 1996; 25: 909-15.
Banares R, Moitinho E, Piqueras B, Casado M, Garcia-Pagan JC, de Diego A, Bosch J. Carvedilol, a new nonselective beta-blocker with intrinsic anti- Alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis. Hepatology 1999; 30: 79-83.
Lebrec D, Hillon P, Munoz C, Goldfarb G, Nouel O, Benhamou JP. The effect of propranolol on portal hypertension in patients with cirrhosis: a hemodynamic study. Hepatology 1982; 2: 523-7.
Abraldes JG, Tarantino I, Turnes J, Garcia-Pagan JC, Rodes J, Bosch J. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis. Hepatology 2003; 37: 902-8.
Perez-Ayuso RM, Pique JM, Bosch J, Panes J, Gonzalez A, Perez R, Rigau J, et al. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. Lancet 1991; 337: 1431-4.
Hoshino S, Shinoura S, Akamine H. Effect of propranolol for the prevention of spontaneous bacterial peritonitis. Am J Gastroenterol 2000; 95: A349.
Perez-Paramo M, Munoz J, Albillos A, Freile I, Portero F, Santos M, Ortiz-Berrocal J. Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites. Hepatology 2000; 31: 43-8.
Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet 1999; 353: 139-42.
Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371: 838-51.